Johns Hopkins scientists report the discovery of a
protein found only in cerebrospinal fluid that they say
might be useful in identifying a subgroup of patients with
multiple sclerosis or identifying those at risk for the
debilitating autoimmune disorder.

MS strikes more than 10,000 Americans each year, most
of whom are women, and causes weakness, numbness, a loss of
muscle coordination and problems with vision, speech and
bladder control. It is a disorder in which the immune
system destroys myelin, the covering of nerves that helps
transmit signals. Cerebrospinal fluid, or CSF, is the
watery fluid that surrounds and cushions the brain and
spinal cord.

The federally funded Johns Hopkins research, reported
in the February issue of the Annals of Neurology, is
important, the researchers say, because unlike other
autoimmune diseases in which the body attacks its own
tissues, MS cannot be diagnosed with a simple blood or
other test.

While it is recognized that there might be several
forms of MS, laboratory-based tests need to be developed to
diagnose these subtypes.

"There is the possibility now that the protein we
identified, 12.5 kDa cystatin, can be used to diagnose MS,
perhaps in its earliest stages, and also to monitor
treatment by measuring its levels in CSF," said Avindra
Nath, a professor in the
Department of
Neurology at the School of Medicine and lead author of
the study.

Working with human CSF, the Johns Hopkins team showed
that 12.5 kDa cystatin is a breakdown product of a larger
protein called cystatin C or 13.4kDa, which in turn blocks
activity of some enzymes, including cathepsin B. Cathepsin
B has been linked to demyelination, the destruction of the
nerve sheath. The term kDa refers to kilodalton, the weight
of one molecule of a substance.

"In fact, those patients who had more of the breakdown
product of 12.5 kDa cystatin also seemed to have the
highest cathepsin B inhibition," Nath said.

The investigators made their finding using a
sophisticated technique called SELDI-time-of-flight mass
spectroscopy that can find one specific protein in a
complex mixture based on its weight. They used it to
examine CSF samples from 29 patients with MS or pre-MS
symptoms such as numbness on one side; 27 patients with
transverse myelitis, a painful inflammation of spinal cord
nerves; 50 infected with the AIDS virus (which can cause
nerve damage); and 27 with other neurological diseases. The
Johns Hopkins scientists analyzed CSF instead of blood
samples because CSF better represents local events in the
brain than does blood, according to Nath. And the high
concentrations of many proteins in the blood can mask
proteins that might be biomarkers for MS, he added.

The team found that the 12.5kDa fragment of cystatin C
occurred in CSF samples from two-thirds of patients with MS
or the pre-MS conditions. Moreover, although total cystatin
C levels in MS patients were not different from control
patients without the disease, patients with MS had a larger
proportion of the 12.5 kDa compared to 13.4 kDa cystatin C
than did other patients. Thus, the presence of the 12.5 kDa
fragment might identify a subgroup of MS patients.

This study was supported by the National Institutes of
Health, National Institute of Neurological Disorders and
Stroke, National Institute on Drug Abuse, National
Institute of General Medical Sciences and by a
Collaborative Center Grant from the National Multiple
Sclerosis Society.